ANRIL, Chromosome 9p21 and Coronary Artery Disease

I had just attended a talk by Dr Ruth McPherson on the topic of “Genetic Insights into Coronary Artery Disease”. She spoke about her genomewide association study (GWAS) which she had recently published in Science. For a quick review of the recent developments in GWAS of CAD, you can refer to my editorial in the European Heart Journal.

GWAS have consistently pointed to chromosome 9p21 and its robust association with CAD. Several replication studies have confirmed this fact. Approximately 25% of Caucasians carry 2 copies of the risk allele and have a 1.5 fold higher risk for CAD. The increased risk associated with this allele is independent of all known CAD risk factors. Thus the identification of region suggests that a novel biological pathway may be involved in atherosclerosis.

The 9p21 locus overlaps a newly annotated antisense noncoding RNA in the INK4 locus splice variant (ANRIL or DQ485453). ANRIL spans 126.3kb and overlaps at its 5’end with CDKN2B (p15INK4b). It consists of 19 exons, of which the first 12 exons are conserved whereas exons 13-19 are subjected to alternative splicing.

It would be exciting to see how the investigations of the 9p21 region would unfold in the near future!